Is DHX16 p.Ser17Ter (c.50C>A) pathogenic?

DHX16 p.Ser17Ter (c.50C>A) is classified Likely pathogenic in DHX16 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-24). Absent from gnomAD v4.1; Associated with neuromuscular disease and ocular or auditory anomalies with or without seizures.

How common is DHX16 p.Ser17Ter (c.50C>A) in the general population?

DHX16 p.Ser17Ter (c.50C>A) is absent from gnomAD v4.1 (gnomAD).

DHX16 p.Ser17Ter

Q: What condition is associated with DHX16 p.Ser17Ter (c.50C>A)?

DHX16 p.Ser17Ter (c.50C>A) is associated with neuromuscular disease and ocular or auditory anomalies with or without seizures (ClinVar).

c.50C>A · VCV4277517

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

neuromuscular disease and ocular or auditory anomalies with or without seizures

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 20
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	phastCons 1
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DHX16
Protein: p.Ser17Ter
Coding: c.50C>A
MANE Select: NM_003587
Type: single nucleotide variant
Location: chr6:30672792 (GRCh38)
Gene constraint: LOEUF 0.716 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.82 · 12 PDB

Full DHX16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neuromuscular disease and ocular or auditory anomalies with or without seizures — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DHX16 p.Thr674Met Pathogenic/Likely pathogenic ★★ same condition
DHX16 p.Arg940Cys Uncertain significance ★★ ⚠ same condition
DHX16 p.Arg956Gln Uncertain significance ★★ ⚠ same condition
DHX16 p.Asp580Gly Uncertain significance ★★ ⚠ same condition
DHX16 p.Glu105Lys Uncertain significance ★★ ⚠ same condition
DHX16 p.Glu678Gly Likely pathogenic ★ same condition
DHX16 c.1126-3T>C Uncertain significance ★ same condition
DHX16 c.447-1G>A Uncertain significance ★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dhx16-p-ser17ter (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown